Global Patent Index - EP 3933036 A1

EP 3933036 A1 20220105 - PROCESS FOR 7-BETA-HYDROXYLATION OF BILE ACID DERIVATIVES

Title (en)

PROCESS FOR 7-BETA-HYDROXYLATION OF BILE ACID DERIVATIVES

Title (de)

VERFAHREN ZUR 7-BETA-HYDROXYLIERUNG VON GALLENSÄUREDERIVATEN

Title (fr)

PROCÉDÉ D'HYDROXYLATION 7-BÊTA DE DÉRIVÉS D'ACIDE BILIAIRE

Publication

EP 3933036 A1 20220105 (EN)

Application

EP 20183693 A 20200702

Priority

EP 20183693 A 20200702

Abstract (en)

A first aspect of the invention relates to a process for 7-beta-hydroxylation of bile acid derivatives comprising: (a) providing a bile acid derivative according to general formula (I); (b) contacting the bile acid derivative according to general formula (I) with at least one cytochrome P450 monooxygenase analog, wherein the cytochrome P450 monooxygenase analog comprises at least two mutations compared to the parent cytochrome P450 monooxygenase; thereby obtaining a bile acid derivative according to general formula (II) as a product, which has a beta-hydroxyl group in position 7. A second aspect of the invention relates to a bile acid derivative according to general formula (II), which has a beta-hydroxyl group in position 7, obtained or obtainable from the process of the first aspect. In a third aspect, the invention is related to a cytochrome P450 monooxygenase analog, wherein the parent cytochrome P450 monooxygenase of the cytochrome P450 monooxygenase analog is cytochrome P450 monooxygenase CYP107D1 (OleP) from Streptomyces antibioticus according to SEQ ID NO: 1, wherein the cytochrome P450 monooxygenase analog comprises at least two mutations compared to the parent cytochrome P450 monooxygenase at positions selected from the group consisting of 84, 240, and 291. A fourth aspect of the invention is related to a polynucleotide encoding the cytochrome P450 monooxygenase analog of the third aspect. In a fifth aspect, the invention is related to a vector comprising the polynucleotide encoding the cytochrome P450 monooxygenase analog of the third aspect. A sixth aspect of the invention relates to a host cell comprising the cytochrome P450 monooxygenase analog of the third aspect and/or the polynucleotide of the fourth aspect, and/or the vector of the fifth aspect.

IPC 8 full level

C12N 9/02 (2006.01); C12P 33/06 (2006.01)

CPC (source: EP)

C12N 9/0077 (2013.01); C12P 33/06 (2013.01)

Citation (applicant)

  • S KULPRECHAT UEDAT NIHIRAT YOSHIDAH TAGUCHI, APPL. ENVIRON. MICROBIOL., vol. 1985, 1985, pages 338
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  • "GenBank", Database accession no. ZP_01773061.1
  • R. K. KUIPERSH.-J. JOOSTENW. J. H. VAN BERKELN. G. H. LEFERINKE. ROOIJENE. ITTMANNF. VAN ZIMMERENH. JOCHENSU. BORNSCHEUERG. VRIEND, PROTEINS, vol. 78, 2010, pages 2101
  • A. LIC. G. ACEVEDO-ROCHAZ. SUNT. COXJ. L. XUM. T. REETZ, CHEMBIOCHEM, vol. 19, 2018, pages 221
  • "UniProt", Database accession no. Q59819
  • T. OMURAR. SATO, J. BIOL. CHEM., vol. 239, 1964, pages 2370
  • F. P. GUENGERICHM. V. MARTINC. D. SOHLQ. CHENG, NATURE PROT., 2009, pages 4
  • E. F. PETTERSENT. D. GODDARDC. C. HUANGG. S. COUCHD. M. GREENBLATTE. C. MENGT. E. FERRIN, J. COMP. CHEM., vol. 25, 2004, pages 1605
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Citation (search report)

  • [X] WO 2020076819 A1 20200416 - INTREXON CORP [US]
  • [X] CN 109055473 A 20181221 - HUNAN BIO ESSENTIAL TECH CO LTD
  • [X] WO 2016016213 A1 20160204 - PHARMAZELL GMBH [DE]
  • [A] US 2001034046 A1 20011025 - MCDANIEL ROBERT [US]
  • [A] KOLLEROV V V ET AL: "Hydroxylation of lithocholic acid by selected actinobacteria and filamentous fungi", STEROIDS, ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY, US, vol. 78, no. 3, 18 January 2013 (2013-01-18), pages 370 - 378, XP028981316, ISSN: 0039-128X, DOI: 10.1016/J.STEROIDS.2012.12.010
  • [AD] GROBE SASCHA ET AL: "Highly selective bile acid hydroxylation by the multifunctional bacterial P450 monooxygenase CYP107D1 (OleP)", BIOTECHNOLOGY LETTERS, KLUWER ACADEMIC PUBLISHERS, DORDRECHT, vol. 42, no. 5, 23 January 2020 (2020-01-23), pages 819 - 824, XP037078322, ISSN: 0141-5492, [retrieved on 20200123], DOI: 10.1007/S10529-020-02813-4
  • [A] FABIO TONIN ET AL: "Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review", BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, vol. 14, 5 February 2018 (2018-02-05), pages 470 - 483, XP055657131, DOI: 10.3762/bjoc.14.33
  • [T] SASCHA GROBE ET AL: "Engineering Regioselectivity of a P450 Monooxygenase Enables the Synthesis of Ursodeoxycholic Acid via 7[beta]-Hydroxylation of Lithocholic Acid", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 60, no. 2, 11 January 2021 (2021-01-11), pages 753 - 757, XP055771624, ISSN: 1433-7851, DOI: 10.1002/anie.202012675

Designated contracting state (EPC)

AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

Designated extension state (EPC)

BA ME

DOCDB simple family (publication)

EP 3933036 A1 20220105

DOCDB simple family (application)

EP 20183693 A 20200702